The major objective of the Mouse Core is to provide a centralized facility to insure the capacity of each participating project lab to produce and maintain transgenic and gene-disrupted mice. All four projects in this proposal will utilize transgenic approaches in their studies. The creation of a Core will result in economy of effort and expense by avoiding duplication of a highly technical skill requiring specialized equipment. The Core will facilitate collaborations between projects. Dedicated space and equipment for ES cell culture and microinjection of eggs and blastocysts has been secured on the Parnassus Campus and adequate animal space is assigned to the Principal Investigator for Core functions. Although the request for support for this Core is new for this grant, we have been operating a functional virtual core in a highly effective manner for the last six months. Most of the mouse lines described in the Progress Report and Preliminary Data sections of the proposal have been generated using the staff and facilities described below.